3K3A-Activated Protein C Variant Does Not Interfere With the Plasma Clot Lysis Activity of Tenecteplase.
3K3A-Activated Protein C Variant Does Not Interfere With the Plasma Clot Lysis Activity of Tenecteplase.
复制标题
3K3A 激活的蛋白 C 变体不会干扰替奈普酶的血浆凝块溶解活性。
DOI：
10.1161/strokeaha.120.028793
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发表时间：
2020
期刊：
影响因子：
8.3
通讯作者：
Griffin,JohnH
中科院分区：
文献类型：
--
作者：
Mukherjee,Purba;Lyden,Patrick;Fernández,JoséA;Davis,ThomasP;Pryor,KentE;Zlokovic,BerislavV;Griffin,JohnH
背景和目的APC的重组工程化突变体3K3A-APC在保留APC抗炎、抗细胞凋亡和神经保护功能的同时，缺乏抗凝特性(10%)，在缺血性卒中的临床试验中具有很好的应用前景。第三代组织型纤溶酶原激活剂替替普酶单次推注的治疗干预有望广泛应用于急性缺血性卒中的治疗。3K3A-APC在服用阿替普酶的中风患者中耐受性良好，体外研究表明3K3A-APC不干扰阿替普酶诱导的血栓溶解。本研究的目的是评价3K3A-APC对替替普酶诱导的凝块溶解的影响。方法在不同剂量的3K3A-APC存在下，观察Tenecteplase介导的凝血酶诱导的人正常混合血浆凝块的溶解。结果3K3A-APC的存在缩短了低浓度替替普酶诱导的血栓溶解时间，但对高浓度替替普酶诱导的血栓溶解时间无明显影响。3K3A-APC对替替普酶的溶栓作用无明显影响。结论3K3A-APC不干扰替替普酶的溶栓作用。
Background and PurposeA recombinant engineered variant of APC (activated protein C), 3K3A-APC, lacks anticoagulant properties (<10%) while preserving APCs anti-inflammatory, anti-apoptotic, and neuroprotective functions and is very promising in clinical trials for ischemic stroke. Therapeutic intervention with single bolus administration of the third-generation tPA (tissue-type plasminogen activator), tenecteplase, is anticipated to be widely adopted for treatment of acute ischemic stroke. 3K3A-APC is well-tolerated in stroke patients dosed with alteplase, and in vitro studies show 3K3A-APC does not interfere with alteplase-induced clot lysis. The purpose of this in vitro study was to assess the influence of 3K3A-APC on tenecteplase-induced clot lysis.MethodsTenecteplase-mediated lysis of thrombin generated plasma clots of human normal pooled plasma was monitored in the presence of varying doses of 3K3A-APC. The effects on fibrinolysis by tenecteplase and alteplase were compared.ResultsThe presence of 3K3A-APC shortened the time for clot lysis induced by tenecteplase at very low levels but not at higher therapeutic concentrations of tenecteplase. Comparisons of alteplase-mediated clot lysis to tenecteplase clot lysis showed that both thrombolytic agents behaved similarly in the presence of 3K3A-APC.ConclusionsThese results indicate that 3K3A-APC does not interfere with tenecteplase’s clot lysis function.